Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells
Iron uptake in the intestinal epithelium is associated with transport of ferrous iron via the DMT1 transporter (SLC11a2; NRAMP2). In later years, uptake of iron from complex sources, such as nanoparticles, has been found to be mediated through endocytosis. Here we propose that iron from the simple s...
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Frontiers Media S.A.
2025-01-01
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| author | Agata Tarczykowska Per Malmberg Nathalie Scheers |
| author_facet | Agata Tarczykowska Per Malmberg Nathalie Scheers |
| author_sort | Agata Tarczykowska |
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| description | Iron uptake in the intestinal epithelium is associated with transport of ferrous iron via the DMT1 transporter (SLC11a2; NRAMP2). In later years, uptake of iron from complex sources, such as nanoparticles, has been found to be mediated through endocytosis. Here we propose that iron from the simple salt ferrous fumarate, a common iron supplement, can be absorbed by clathrin-mediated endocytosis. We used siRNA to silence DMT1 transporter expression, pharmacological inhibition of endocytosis, and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to show that iron uptake from ferrous fumarate can be mediated by both transport via DMT1 and by clathrin-dependent endocytosis in Hutu-80 cells. Iron uptake (ferritin L) from ferrous fumarate (0.5 mM, 24 h) in DMT1 silenced cells was significantly decreased (60% ± 11%) in comparison to iron controls while a 1-h dose of ferrous fumarate (0.5 mM) significantly decreased ferritin L formation in the presence of the clathrin inhibitor chlorpromazine (61% ± 10%, in post-confluent cells and 37% ± 9% in non-confluent cells). A pilot showed a similar trend for Ferritin (H) levels (confluent cells) and for total cellular iron load (non-confluent cells). ToF-SIMS analysis revealed diminished membrane-associated iron load in endocytosis-inhibited ferrous fumarate treated cells. The reported results support a clathrin-mediated endocytosis mechanism for uptake of iron from ferrous fumarate in addition to iron uptake by DMT1. More studies are needed to understand what determines which uptake mechanism are employed and to which extent. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-f8c0964389654e879f85c715db4410be2025-01-27T05:14:38ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-01-011210.3389/fmolb.2025.14605651460565Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cellsAgata Tarczykowska0Per Malmberg1Nathalie Scheers2Division of Food and Nutrition Science, Department of Life Sciences, Chalmers University of Technology, Goteborg, SwedenDivision of Chemistry and Biochemistry, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Goteborg, SwedenDivision of Food and Nutrition Science, Department of Life Sciences, Chalmers University of Technology, Goteborg, SwedenIron uptake in the intestinal epithelium is associated with transport of ferrous iron via the DMT1 transporter (SLC11a2; NRAMP2). In later years, uptake of iron from complex sources, such as nanoparticles, has been found to be mediated through endocytosis. Here we propose that iron from the simple salt ferrous fumarate, a common iron supplement, can be absorbed by clathrin-mediated endocytosis. We used siRNA to silence DMT1 transporter expression, pharmacological inhibition of endocytosis, and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to show that iron uptake from ferrous fumarate can be mediated by both transport via DMT1 and by clathrin-dependent endocytosis in Hutu-80 cells. Iron uptake (ferritin L) from ferrous fumarate (0.5 mM, 24 h) in DMT1 silenced cells was significantly decreased (60% ± 11%) in comparison to iron controls while a 1-h dose of ferrous fumarate (0.5 mM) significantly decreased ferritin L formation in the presence of the clathrin inhibitor chlorpromazine (61% ± 10%, in post-confluent cells and 37% ± 9% in non-confluent cells). A pilot showed a similar trend for Ferritin (H) levels (confluent cells) and for total cellular iron load (non-confluent cells). ToF-SIMS analysis revealed diminished membrane-associated iron load in endocytosis-inhibited ferrous fumarate treated cells. The reported results support a clathrin-mediated endocytosis mechanism for uptake of iron from ferrous fumarate in addition to iron uptake by DMT1. More studies are needed to understand what determines which uptake mechanism are employed and to which extent.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1460565/fullDMT1endocytosisironHutu-80Caco-2ferrous fumarate |
| spellingShingle | Agata Tarczykowska Per Malmberg Nathalie Scheers Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells Frontiers in Molecular Biosciences DMT1 endocytosis iron Hutu-80 Caco-2 ferrous fumarate |
| title | Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells |
| title_full | Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells |
| title_fullStr | Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells |
| title_full_unstemmed | Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells |
| title_short | Uptake of iron from ferrous fumarate can be mediated by clathrin-dependent endocytosis in Hutu-80 cells |
| title_sort | uptake of iron from ferrous fumarate can be mediated by clathrin dependent endocytosis in hutu 80 cells |
| topic | DMT1 endocytosis iron Hutu-80 Caco-2 ferrous fumarate |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1460565/full |
| work_keys_str_mv | AT agatatarczykowska uptakeofironfromferrousfumaratecanbemediatedbyclathrindependentendocytosisinhutu80cells AT permalmberg uptakeofironfromferrousfumaratecanbemediatedbyclathrindependentendocytosisinhutu80cells AT nathaliescheers uptakeofironfromferrousfumaratecanbemediatedbyclathrindependentendocytosisinhutu80cells |